Improved Oral Bioavailability and Brain Distribution of Hesperidin via Cochleate Formulation: Statistical Optimization and Pharmacokinetic Study

Abstract

Hesperidin, a flavanone, exhibits antioxidant, anti-inflammatory, and anti-amyloidogenic properties, making it a promising candidate for the treatment of Alzheimer’s disease. The hesperidin possesses poor solubility, and its oral bioavailability is < 20%. Therefore, hesperidin cochleates (HC) were prepared using the trapping method of calcium ions into preformed liposomes to improve oral bioavailability.

The HC formulation was statistically optimized by applying a 3-level factorial design. Optimum cochleates were observed, with an average particle size of 398.9 nm, a zeta potential of -39.1 mV, and an entrapment efficiency of 92.2%, respectively. The in vitro release of hesperidin from cochleates (Batch 15) was 97% in phosphate buffer at pH 7.4 after 24 h. The HC formulation exhibited a 1% release at a gastric pH of 1.2, indicating its stability in the stomach, allowing the formulation to reach the absorption site.

In Wistar rats, a comparative pharmacokinetic study was conducted between hesperidin liposomes and HC. Hesperidin concentration was 2.21-fold higher in plasma and 1.2-fold higher in the brain after cochleates administration than in the liposomal formulation and more than 25-fold greater than plain API. Thus, cochleates may be superior oral carriers for hesperidin, improving its oral bioavailability for the treatment of Alzheimer’s disease.

Continue reading here

Kaur, K., Kulkarni, Y.A. & Wairkar, S. Improved Oral Bioavailability and Brain Distribution of Hesperidin via Cochleate Formulation: Statistical Optimization and Pharmacokinetic Study. AAPS PharmSciTech 27, 59 (2026). https://doi.org/10.1208/s12249-025-03297-z

Read more articles on Hesperidin here:

• Development and characterisation of polymeric solid dispersed systems of hesperidin, obtained by centrifugal fibre formation
• Nanostructured Lipid Carriers (NLC)-Based Topical Formulation of Hesperidin for Effective Treatment of Psoriasis
• Budesonide-Loaded Solid Lipid Nanoparticle Engrossed Hydrogel